Certain 3,5-Dichlorophenyl compound as an antifungal agent

ABSTRACT

An agricultural composition which comprises as an active ingredient a compound represented by the following formula:   AND WHICH SHOWS A STRONG ANTI-FUNGAL ACTIVITY AGAINST PHYTOPATHOGENIC FUNGI OF Sclerotinia and Botrytis genera without any appreciable toxicity to crop plants or to mammals and fish.

United States Patent [191 Tottori et a].

[54] CERTAIN 3,5-DICHLOROPHENYL COMPOUND AS AN ANTIFUNGAL AGENT [75] Inventors: Nobumasa Tottori; Yasuhisa Asano,

both of Minoo; Minoru Ueda; Osamu Kirino, both of Takarazuka; Shigehiro Ooba, Kobe; Akira Fujinami, Ashiya; Toshiaki Ozaki, Toyonaka, all of Japan [73] Assignee: Sumitomo Chemical Company,

Limited, Japan [22] Filed: Nov. 1, 1973 [211 Appl. No.: 411,838

[30] Foreign Application Priority Data Nov. 2, 1972 Japan 47-109890 [52] US. Cl. 424/274 [5]] Int. Cl. A01N 9/22 [58] Field of Search 424/274; 260/326 [56} References Cited UNITED STATES PATENTS 3,261,845 7/1966 Bockstahlcr 424/274 51 Sept. 16, 1975 Primary ExaminerV. D. Turner Attorney, Agent, or F irmStewart and Kolasch, Ltd.

[5 7 ABSTRACT An agricultural composition which comprises as an active ingredient a compound represented by the following formula:

genera without any appreciable toxicity to crop plants or to mammals and fish.

6 Claims, No Drawings 1 CERTAIN 3,5-DICHLOROPHENYL COMPOUND AS AN ANTIFUNGAL AGENT which exhibits a remarkable anti-fungal activity against phyto-pathogenic fungi, particularly of the Sclerotinia and Botrytis genera, without any appreciable toxicity to crop plants or to mammals and fish.

The said 3,5-dichlorophenyl compound [I] is known and described to be useful as a veterinary medicament [cf. U.S. Pat. Nos. 3,215,597 and 3,261,845]. Further, it is described that N-4-fluorophenyl-3,6epoxyhexahydrophthalimide similar to the 3,5-dichlorophenyl compound [I] in chemical structure has an acaricidal activity [cf. U.S. Pat. No. 3,261,845]. However, no literature has ever suggested the practical use of the 3,5 dichlorophenyl compound [I] as an active ingredient in agricultural compositions, particularly in fungicidal compositions against phyto-pathogenic fungi.

As the result of extensive studies, it has now been found that the 3,5-dichlorophenyl compound [I] exhibits a remarkable anti-fungal activity against phytopathogenic fungi, particularly of the Sclerotinia and Botrytis genera. It has also been found that the 3,5 dichlorophenyl compound does not cause any phytotoxicity on crop plants when applied in an amount which is sufficient to exert anti-fungal activity. It has further been found that the 3,5-dichlorophenyl compound [I] shows an extremely low toxicity with regard to mammals and fish.

In this connection, it should be noted that a number of compounds closely related to the 3,5-dichlorophenyl compound [I] in chemical structure have been known but their anti-fungal activity is so weak as to preclude any practical application.

According to the present invention, there is provided an agricultural composition, especially a fungicidal composition in a preparation form such as dusts, Wettable powders, emulsifiable concentrates, sprays, aerosols, fumigants, pellets and granules, which comprises the 3,5-dichlorophenyl compound [I] alone or in association with one or more gaseous, solid or liquid carriers of the types commonly used in fungicidal compositions. Besides the 3,5-dichlorophenyl compound [I], the composition may contain one or more known fungicides (e.'g. Blast-icidin S, Kasugamycin, Polyoxin, Cellocidin, Chloramphenicol, Validamycin, Streptomycin, Griseofulvin, cycloheximide, pentachloronitrobenzene, pentachlorophenol and its salts, 2,6-dichloro-4- nitroaniline, zinc ethylenebis(dithiocarbamate), zinc dimethyldithiocarbamate, manganese ethylenebis(dithiocarbamate), bis(dimethylthiocarbamoyl) disulfide, 2,4,5 ,6tetrachloroisophthalonitrile, 2,3-dichlorol ,4- naphthoquinone, tetrachloro-p-benzoquinone, tetrachlorophthalide, p-dimethylaminobenzenediazosodium sulfonate, 2-( l-methylheptyl)-4,6-dinitrophenylcrotonate, 2-heptadecylimidazoline acetate, 2,4- dichloro-6-(o-chloroanilino)-Striazine, dodecylguanidine acetate, 6-methyl-2,3-quinoxalinedithiol cyclic S,S-dithiocarbonate, N-trichloromethylthio-4- cyclohexene l ,Z-dicarboximide, N-( l, l ,2,2- tetrachloroethylthio)-4-cyclohexenel ,2- dicarboximide, 3-(3,5-dichlorophenyl)-5,5- dimethyloxazolidinedione-2,4, N-( 3 ,5- dichlorophenyl )-maleimide, N-( 3 ,5-dichlorophenyl succinimide, N-( 3 ,5-dichlorophenyl )-itaconimide, 2,3-dihydro-5-carboxanilide, 6-methyll ,4-oxazine, 1- (N-butylcarbamoyl)-2- methoxycarbonylaminobenzimidazole, 2-( 4 thiazolyl)-benzimidazole, l,2-bis( 3-ethoxycarbonyl-2- thioureido )-benzene, l,2-bis( 3-methoxycarbonyl-2- thioureido)-benzene, 2-amino-5-mercaptothiadiazole, 2-aminothiadiazole, O-butyl-S-benzyl-S-ethylphorodithioate, O-ethyl-S,S-diphenylphosphorodithioate, 0,0- diisopropyl-S-benzyophosphorothioate, 0,0-dimethyl- O-(3-methyl-4-nitrophenyl)-phosphorothioate, S-[ 1,2- bis(ethoxycarbonyl )ethyl ]-0,0-dimethylphosphorodi thioate, 0,0-dimethyl-S-(Nmethylcarbamoylmethyl)- phosphorodithioate, 0,0-diethyl-O-( 2-isopropyl-6- methyl-4-pyrimidyl )-thiophosphate, 1 ,3- bis(carbamoylthio)-2-(N,N-dimethylamino)propane hydrochloride, 3,4-dimethylphenyl-N- methylcarbamate, l-naphthyl-N-methylcarbamate, 2- chloro-4,6-bis(ethylamino)-S-triazine, 2,4-dichlorophenoxyacetic acid and its salts and esters, 2-methyl-4- chlorophenoxyacetic acid and its salts and esters, 2,4- dichlorophenyl-4-nitrophenyl ether, N-(3,4-dichlorophenyl )-propionamide, 3-( 3 ,4'-dichlorophenyl)-1,1- dimethylurea, 4-chloroben2yl-N,N-dimethylthiol carbarnate, 1,1 -dimethyl-4,4'-bipyridium dichloride, 2,4,- 6-trichlorophenyl-4'-nitrophenyl ether, N'-(2-methyl- 4-chlorophenyl)-N,N-dimethylformamidine, N,N-diallyl-2-chloroacetamide, ethyl(or cyclohexyl) B-(2,4- dichlorophenoxy)-acrylate, S-n-heptyl-S-(p-tbutylbenzyl)-N-(3'pyridyl)-imidodithiocarbonate, S- n-butyl-S"(p-t-butylbenzyl)-N-(3pyridyl)-imidodithiocarbonate, etc.). The composition may also contain one or more materials known to be active as bacteri' cides, insecticides, nematocides, acaricides, herbicides, fertilizers, soil conditioners or plant growth regulators. Typical examples of the agricultural composition according to this invention are:

a. Dusts obtained by dispersing the 3,5- dichlorophenyl compound [I] as the active ingredient in a concentration of 0.1 to 30 percent by weight in an inert carrier (e.g. talc, diatomaceous earth, wood flour, clay).

b. Wettable powders obtained by dispersing the 3,5- dichlorophenyl compound [I] as the active ingredient in a concentration of 0.2 to percent by weight in an inert adsorbent carrier (e.g. diatomaceous earth) together with a wetting and/or dispersing agent such as an alkali metal salt of a long aliphtic sulfate chain, a partly neutralized sulfuric acid derivative of either a petroleum oil or a natural occurring glycerine or a condensation product of an alkylene oxide with an organic acid.

c. Emulsifiable concentrates obtained by dispersing the 3,5-dichlorophenyl compound [1] as the active ingredient in a concentration of l to 50 percent by weight in an organic solvent (e.g. dimethylsulfoxide) plus a wetting and/or dispersing agent such as an alkali metal salt of a long aliphatic sulfate chain, a partly neutralized sulfuric acid derivative of either a petroleum oil or a natural occurring glycerine or a condensation product of an alkylene oxide with an organic acid.

d. Compositions of the 3,5-dichlorophenyl compound [l] formulated in the manner commonly employed in the art for the preparation of fungicidal fumigants.

More specific examples of the agricultural composition of this invention are shown below. In these examples, parts and are by weight.

EXAMPLE 1 Preparation of wettable powder:

The 3,5-dichlorophenyl compound [I], i.e. N-(3',5- dichlorophenyl)-7oxabicyclo( 2,2,1 )heptane-2,3- dicarboximide (M.P. l54 155C), (50 parts), a wet ting agent (an alkylbenzenesulfonate) parts) and diatomaceous earth (45 parts) are crushed and mixed well to form a wettable powder preparation containing 50 of the active ingredient. The wettable powder preparation is diluted with water and then applied.

EXAMPLE 2 Preparation of dust:

The 3,5-dichlorophenyl compound [I] (3 parts) and clay (97 parts) are crushed and mixed well to form a dust preparation containing 3 percent of the active ingredient. The dust preparation is applicable as such.

EXAMPLE 3 Preparation of emulsifiable concentrate: The 3,5-dichlorophenyl compound [I] 10 parts), di-

0 ompound N o methylformamide (70 parts), toluene 10 parts) and an emulsifier (polyoxyethylenedodecylphenol ether) (10 parts) are mixed well to form an emulsifiable concentrate preparation containing 10 percent of the active ingredient. The emulsifiable concentrate preparation is diluted with water and then applied.

EXAMPLE 4 Preparation of fumigant:

The 3,5-dichlorophenyl compound [I] (90 parts) a nitrite (3 parts), wood flour (2 parts) and diatomaceous earth (5 parts) are pulverized and mixed well to 'form a fumigant preparation containing 90 percent of the active ingredient. The fumigant preparation is applied by fumigating on a heating fumigator.

EXAMPLE 5 Preparation of complex wettable powder:

The 3,5-dichlorophenyl compound [I] (40 parts), S- n-butyl-S p-t-butylbenzyl )-N-( 3-pyridyl )-dithiocarbonate (10 parts), diatomaceous earth parts) and a wetting agent (calcium ligninsulfonate) (5 parts) are pulverized and mixed well to form a complex wettable powder preparation containing percent of the active ingredients. The complex wettable powder preparation is diluted with water and then applied.

Some of the test results which support the anti-fungal activity of die 3,5-dichlorophenyl compound [I] are shown below.

The known compounds used in the following tests for comparison are as follows:

I Disclosed in U-S. patent 3, 45

' Disclosed in U.S. patent c0 3,261,845

C1 c0 Disclosed in U.S. patent N 3,2 1,845

-Continued Comnound No. Structure I Y Remarks Disclosed in 6 U-S. patent Disclosed in 7 U S pat ent '3 261 845 Disclosed in 8 U-S- patent Disclosedin 9 U S pa t enc TEST, 1 Infectious index 0 Infectious area I v i I 0 I None A test compound in wettable powder form was di- '1 Up to 1/5 of the ma! area of the'inoculated luted with water and a l' t pp kldney r seedllmgs l 2 More than 1/5 and up to 2/5 of the total area cultured lllPOIS of 15 cm in diameter and grown up to er the inoculated leaf the three trifoliate stage at a dose of 10 ml of the dilu- More t 2/5 and up to l of the we! arc-u t Aft f h a x l.- d. of the inoculated leaf p PO er our Ours 4 p More than 3/5 and up to 4/5 of the total area inoculum of Sclerotinia sclerotiorum (diameter, 5 mm) o h n u a daf was inoculated on the leaves. The infectious area at the 5 f s leaves was observed 3 days thereafter, and the size of the diseased spot was measured. The degree of damage 40 The degree of disease-preventing effect was calcuwas calculated according to the following equation: lated according to the following equation:

Degree of 8110 of diseased spots 817.0 of diseased spots di in untreated plot in treated plot Preventing Size of diseased spots x 00 effect in untreated plot Infection Number of The results are shown in Table 1, from which it is Dcgrcc f damage 'Pi i fi clear that the 3,5-dichlorophenyl compound [I] has a Total number of leaves stronger anti-fungal activity than the analogous compounds such as the corresponding monochlorinated,

wherein the infectious index was determined on the foldichlorinated, trichlorinated and dinitrated comlowing criteria; pounds.

Table 1 Second leaf Third leaf Concent- T m Compound ration Degree Degree of Degree Degree of (ppm) of diseaseof diseasedamagc preventing damage preventing effect (71) CffCC(,( /v) Present invention 7 Compound [I] 500 0.0 ()0 I00 I 100 0.0 100 0.0 l00 Comparison Compound No. l 500 4.9 2 4.9 2 I00 5.0 0 5.0 0 Compound No. 2 500. 1.3 74 L9 62 10(1 4.6 8 4.9 2

Table l-Continued Test Compound Conccnt- Second Iczif Third leaf ration (ppm) Degree Degree of Degree Degree of of diseaseof diseasedamagc preventing W damage preventing effect /I efiectU/I Compound No. 3 500 5.0 5.0 0 I00 5.0 0 5,0 0 Compound No. 4 500 5.0 0 5.0 0 I00 5.0 0 5.0 0 Compound No. 5 500 4.9 2 5.0 0 I00 5.0 (I, 5.0 0 Compound No. 6 500 4.8' 4 4.9 2 I00 5.0 0 5.0 0 Compound No. 7 500 4.7 6 4.7 6 I00 50 0 5.0 0 Compound No. X 500 4.9 2 5.0 0 I00 5.0 0 5.0 V 0 Compound No. 9 500 4.9 2 4}) 2 100 5.0 0 5.0 0

Untreated 5.0 5,0

TEST 2 Infectious index Infectious area Kidney bean seedlings cultured in pots of9 em in di- 25 dose of 100 liters 'of the dilution per are. After seventeen hours from Y thetreatments in both cases, a

myeeIium-di sc-inoeulum of Sclerotinia sclerotiorum was inoculated o'n the surface and the reverse of the leaves. The infectious areaat the leaves was observed 0 None I V Qnlyaround the inoculated parts 2 lUpfto I of the total area of the inoculated 3 More than H5 and up to 2/5 of the total area of the inoculated leaf 4 More than 2/5 and up to 3/5 of the total area of the inoculated leaf 5 More than 3/5 of the total area of the inoculated leaf The results are shown in Table 2, from which it can 35 be understood that the 3,5-dichlorophenylcompound [I] exerts 'an excellent anti-fungal activity not only when applied in'a wettable powder form but also when applied in a fumigant form.

Table 2 I i '1 I Plot Tcst compound Dose Degree of damage I l I Inoculated Inoculated on surface on reverse Fumigation Compound [I] 500 mg/m 0.0 0.0 I00 "l 4 0.0 0.4 mg/m 0.0 1.0

Foliage Compound I 100 l./l0 a 0.0 0.0

' (as I000 fold dilu- "tion of 71 wettable powder) Untreated 5.0 5.0

4 days. thereafter, and the degree of damage was calcu- TEST 3 lated according to the following equation:

2 Infection x Number of index leaves Degree of damage Total number of leaves wherein the infectious index. was determined on the following criteria:

leaves was observed 4 days thereafter, and the size of the diseased spot was measured. The degree of damage and the degree of disease-preventing effect were calculated as in Test 1.

The results are shown in Table 3, from which it is apparent that the 3,5-dichlorophenyl compound [I] has a stronger anti-fungal activity than the analogous compounds such as the corresponding monochlorinated,

As understood from the above test results, the 3,5- dichlorophenyl compound [I] is useful for the control and prevention of such plant diseases as Sclerotinia rot and Botrytis gray mold of vegetables and field crops.

The 3,5-dichlorophenyl compound [I] may be applied as such. From the practical viewpoint, however, it is usually employed in the form of compositions in association with any agriculturally acceptable inert carrier or diluent as well as any surface active agent or wetting agent. The concentration of the active ingredient in the compositions may be from about 0.1 to percent by weight, although such is not essential.

What is claimed is:

1. A method for preventing plat diseases caused by phyto-pathogenic fungi selected from the group consisting of the genera Sclerotinia and Botrytis which comprises applying to said fungi a fungicidally effective amount of a 3,5-dichlorophenyl compound of the formula:

N- co 2. The method according to claim 1, wherein the 3,5- dichlorophenyl compound is applied to said fungi in the form of a composition comprising said compound and an inert carrier.

3. The method according to claim 2, wherein the concentration of the 3,5-dichlorophenyl compound in said composition is 0.1 to 90 percent by weight.

4. The method according to claim 2, wherein said inert carrier is an organic solvent for the 3,5- dichlorophenyl compound.

5. The method according to claim 3, wherein the phyto-pathogenic fungus is Sclerotinia sclerotiorum.

6. The method according to claim 3, wherein the phyto-pathogenic fungus is Botrytis cinerea. 

1. A METHOD FOR PREVENTING PLAT DISEASES CAUSED BY PHOTOPATHOGENIC FUNGI SELECTED FROM THE GROUP CONSISTING OF THE GENERA SCLEROTINIA AND BOTRYTIS WHICH COMPRISES APPLYING TO SAID FUNGI A FUNGICIDALLY EFFECTIVE AMOUNT OF A 3,5DICHLOROPHENYL COMPOUND OF THE FORMULA:
 2. The method according to claim 1, wherein the 3,5-dichlorophenyl compound is applied to said fungi in the form of a composition comprising said compound and an inert carrier.
 3. The method according to claim 2, wherein the concentration of the 3,5-dichlorophenyl compound in said composition is 0.1 to 90 percent by weight.
 4. The method according to claim 2, wherein said inert carrier is an organic solvent for the 3,5-dichlorophenyl compound.
 5. The method according to claim 3, wherein the phyto-pathogenic fungus is Sclerotinia sclerotiorum.
 6. The method according to claim 3, wherein the phyto-pathogenic fungus is Botrytis cinerea. 